Journal of Medical Virology 82:929–933 (2010) Association of Cytokine Genetic Polymorphisms With the Humoral Immune Response to Recombinant Vaccine Against HBV in Infants Luciana Conci Macedo, Aline Paula Isolani, Jeane Eliete Laguila Visentainer, and Ricardo Alberto Moliterno* Clinical Analysis Department, Maringa´State University, Maringa´, Parana´, Brazil The prevention of hepatitis B by vaccination is one the most efficient tools to avoid the transmission of the virus, although a consider- able variability to the anti-HBsAg antibody response has been described. Recently, poly- morphisms of cytokine regulating genes have been described which seem to influence the immune response to various antigens. This article’s objective was to evaluate the influence of cytokine genetic polymorphisms onto the humoral immune response to hepatitis B vaccine in infants. Vaccinated children were classified according to the level of anti-HBsAg antibody titles. The genotyping for TNF (308), TGFB1 (þ869, þ915), IL-10 (1082, 819, 592), IL-6 (174), and IFNG (þ874) was accomplished by the PCR-SSP technique. The TNF (308) allele A presented a lower but not statistically signifi- cant frequency at 5% level in high responder patients (3.7% vs. 12.3%, P ¼ 0.0919). The same was seen for the TNF (308) genotype GA (7.4% vs. 24.5%, P ¼ 0.0757). Further studies in other populations and evaluation of a greater number of individuals may contribute for a better under- standing of the cytokine gene polymorphism influence in general and TNF polymorphism more specifically in the humoral immune response to the HBsAg vaccination in newborn children. J. Med. Virol. 82:929 – 933, 2010. ß 2010 Wiley-Liss, Inc. KEY WORDS: antibodies; HBsAg; hepatitis B; TNF INTRODUCTION The infection by the hepatitis B virus (HBV) appears under different forms of evolution, ranging from the asymptomatic and self-limited infection to the chronic state, which can develop into chronic hepatitis, cirrhosis, and hepatic-cellular carcinoma [Moradpour and Wands, 1995; Thomas and Strickland, 2000]. It is estimated that the virus contaminates 350 million people in the whole world, forming a reservoir, which facilitates the spreading of the disease [Kane, 1995]. The Health Ministry estimates that 1% of the Brazilian population has chronic diseases related to HBV [Brasil, 2008; Ferreira, 2004]. The prevention of hepatitis B by vaccination is one of the most efficient tools to avoid the transmission of the virus. Two recombinant vaccines derived of yeasts were licensed in 1987. They contain the largest surface protein of the HBV (protein S, HBsAg), and were produced by Merck Sharp Dohme and Smith Kline Beecham, respectively [Granovski, 1997]. The Instituto Butantan developed and is producing the national vaccine Butang 1 against hepatitis B through genetic engineering techniques, using the Hansenulla poly- morpha yeast [Hieu et al., 2002]. However, the production of antibodies in children vaccinated with the national vaccine Butang is not homogeneous. Isolani et al. [2006] demonstrated that approximately 68% and 32% of the children vaccinated are respectively responders (anti-HBs titers between 11 and 1,000 mUI/ml), and high responders (anti-HBs titers higher than 1,000 mUI/ml) to this vaccine. Various exogenous (nutrition, diseases) and endogenous factors (age, gender, and genetic background) may affect the outcome of an anti-HBsAg vaccination [Van Loveren et al., 2001]. Recently, polymorphisms of genes of cytokine regu- lating regions have been described, which seem to correlate with its production [Turner et al., 1997; Awad et al., 1998; Fishman et al., 1998; Pravica et al., 1999; Meenagh et al., 2002]. Due to the influence exerted in the production of cytokines, these polymorphisms can *Correspondence to: Ricardo Alberto Moliterno, Av. Colombo, 5790, Maringa ´ Parana ´ 87020-900, Brazil. E-mail: ramoliterno@uem.br Accepted 18 December 2009 DOI 10.1002/jmv.21762 Published online in Wiley InterScience (www.interscience.wiley.com) ß 2010 WILEY-LISS, INC.